The phosphorylation of nonhistone chromosomal proteins (NHCP) appears to exert a regulatory influence on transcription in eukaryotic cells. The recent discovery that cordycepin (3'-deoxyadenosine) can inhibit normal and neoplastic nuclear protein kinase activities in vitro has prompted an investigation of the role of phosphorylation in the action of this and related drugs. The phosporylation of NHCP in vitro in isolated nuclei will be used to study the effect that cordycepin has on various classes of NHCP. These studies will be extended to L1210 cells in vitro to correlate the effects of cordycepin on nuclear phosphorylation and nRNA synthesis. The latter system will also allow a determination of the effect that the adenosine deaminase inhibitor, 2'-deoxycoformycin, has on the action mediated by cordycepin on the phosphorylation of NHCP. Further analysis of NHCP from rat liver will be performed in order to isolate those NHCP which stimulate transcription via RNA polymerase II in vitro. Characterization of stimulatory NHCP will be performed with specific antineoplastic drugs as pharmacological probes of their molecular sites of action in a cell-free transcription system.